-
作者：Sundararamana, Sesh A.; Miller, Justin J.; Daleya, Ellora C.; O'Briena, Kelsey A.; Kasakc, Paulina; Danielsd, Abigail M.; Edwardse, Rachel L.; Heidelg, Kenneth M.; Bagueg, Darean A.; Wilsonh, Madeleine A.; Koelperh, Andrew J.; Kourtoglouh, Elexi C.; Whiteh, Alex D.; Augusth, Sloan A.; Appleh, Georgia A.; Rouambah, Regis W.; Durandh, Anthony J.; Estebh, John J.; Mulleri, Florian L.; Johnsonh, R. Jeremy; Hoopsh, Geoffrey C.; Dowdg, Cynthia S.; John, Audrey R. Odom
作者单位：University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Thomas Jefferson University; University of Pennsylvania; Washington University (WUSTL); George Washington University; Butler University; University of Pennsylvania
摘要：The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency ...
-
作者：Xie, Yufeng; Kuai, Lu; Peng, Qi; Wang, Qian; Wang, Han; Li, Xiaomei; Qi, Jianxun; Ding, Qiang; Shi, Yi; Gao, George F.
作者单位：Tsinghua University; Chinese Academy of Sciences; Institute of Microbiology, CAS; Peking University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Chinese Academy of Medical Sciences - Peking Union Medical College
摘要：The Mpox virus (MPXV) is an orthopoxvirus that caused a global outbreak in 2022. The poxvirus DNA polymerase complex is responsible for the replication and integrity of the viral genome; however, the molecular mechanisms underlying DNA replication fidelity are still unclear. In this study, we determined the cryoelectron microscopy (cryo-EM) structures of the MPXV F8-A22-E4 polymerase holoenzyme in its editing state, in complex with mismatched primer-template DNA and DNA containing uracil deoxy...
-
作者：Straub, Joshua S.; Patel, Manisha L.; Nowotarski, Mesopotamia S.; Rao, Lokeswara; Turiansky, Mark E.; Fisher, Matthew P. A.; Helgeson, Matthew E.
作者单位：University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara
摘要：Differential isotope effects are an emerging tool for discovering possible nontrivial quantum mechanical effects within biological systems. However, it is often nearly impossible to elucidate the exact mechanisms by which a biological isotope effect manifests due to the complexity of these systems. As such, one proposed in vitro system of study for a quantum isotope effect is calcium phosphate aggregation, where symmetric calcium phosphate molecular species, known as Posner molecules, have bee...
-
作者：Antal, Botond B.; van Nieuwenhuizen, Helena; Chesebro, Anthony G.; Strey, Helmut H.; Jones, David T.; Clarke, Kieran; Weistuch, Corey; Ratai, Eva-Maria; Dill, Ken A.; Mujica-Parodi, Lilianne R.
作者单位：State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; State University of New York (SUNY) System; Stony Brook University; Mayo Clinic; University of Oxford; Memorial Sloan Kettering Cancer Center; The Santa Fe Institute
摘要：Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal landmarks of brain aging starting in midlife (40s). Compariso...
-
作者：Liu, Boqiang; Shen, Hao; He, Jing; Jin, Binghan; Tian, Yuanshi; Li, Weiqi; Hou, Lidan; Zhao, Weijun; Nan, Junjie; Zhao, Jia; Shen, Jiliang; Yu, Hong; Wang, Yifan; Shan, Ge; Shi, Liang; Cai, Xiujun
-
作者：Liu, Daoming; He, Jun; Li, Qi; Zhang, Xiao; Wang, Yongsheng; Sun, Quanguang; Wang, Wenhui; Zhang, Menglong; Wang, Yunlong; Xu, Haosen; Fang, Liang; Jiang, Ling; Liu, Shijia; Chen, Liangming; Tian, Yunlu; Liu, Xi; Wang, Ruyi; Zhang, Zhengguang; Chern, Mawsheng; Dong, Xiaoou; Wang, Haiyang; Liu, Yuqiang; Ronald, Pamela C.; Wan, Jianmin
作者单位：Nanjing Agricultural University; Chinese Academy of Agricultural Sciences; Institute of Plant Protection, CAAS; Nanjing Agricultural University; University of California System; University of California Davis; University of California System; University of California Davis; Chinese Academy of Agricultural Sciences; Institute of Crop Sciences, CAAS; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI
摘要：Plants are subject to attack by diverse pests and pathogens. Few genes conferring broad-spectrum resistance to both insects and pathogens have been identified. Because of the growth-defense tradeoff, it is often challenging to balance biotic stress resistance and yield for crops. Here, we report that OsWRKY36 suppresses the resistance to insects and pathogens via transcriptional repression of Phenylalanine Ammonia Lyases (PALs), a key enzyme in phenylpropanoid pathway in rice. Knocking out OsW...
-
作者：Lust, Katharina; Tanaka, Elly M.
作者单位：Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA)
摘要：Axolotls are amphibian models for studying nervous system evolution, development, and regeneration. Tools to visualize and manipulate cells of the axolotl nervous system with high-efficiency, spatial and temporal precision are therefore greatly required. Recombinant adeno-associated viruses (AAVs) are frequently used for in vivo gene transfer of the nervous system but virus-mediated gene delivery to the axolotl nervous system has not yet been described. Here, we demonstrate the use of AAVs for...
-
作者：Saxena, Tanvi; Quan, Anan; Chan, Erica; Kozlova, Nina; Matai, Latika; Lee, Jonathan D.; Rupaimoole, Rajesha; Beca, Francisco; Muranen, Taru; Slack, Frank J.
作者单位：Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Bayer AG; Bayer Healthcare Pharmaceuticals; Merck & Company
摘要：Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript (TRIDENT), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non-small cell lung cancer. Knocking down TRIDENT leads to decreased t...
-
作者：VanDerwarker, Amber M.; Thakar, Heather B.; Hirth, Kenneth; Domic, Alejandra I.; Harper, Thomas K.; George, Richard J.; Johnson, Emily S.; Newhall, Victoria; Scheffler, Timothy E.; McCool, Weston C.; Wann, Kevin; Gaut, Brandon S.; Kistler, Logan; Kennett, Douglas J.
作者单位：University of California System; University of California Santa Barbara; Texas A&M University System; Texas A&M University College Station; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California Los Angeles; Utah System of Higher Education; University of Utah; University of California System; University of California Irvine; Smithsonian Institution; Smithsonian National Museum of Natural History
摘要：Molecular research suggests that avocados (Persea americana Mill.) were domesticated multiple times in the Americas. Seed exchange, hybridization, and cloning have played an essential role across their wild distribution from Mexico to South America to create the modern varieties of today. Archaeological sites with well- preserved and directly radiocarbon- dated botanical assemblages are rare, however, so we know very little about the complexities of the domestication process. Here, we define a...
-
作者：Carmona-Garcia, Javier; Saiz-Lopez, Alfonso; Mahajan, Anoop S.; Wang, Feiyue; Borrego-Sanchez, Ana; Acuna, A. Ulises; Cuevas, Carlos A.; Davalos, Juan Z.; Feinberg, Aryeh; Spolaor, Andrea; Ruiz-Lopez, Manuel F.; Francisco, Joseph S.; Roca-Sanjuan, Daniel
作者单位：University of Valencia; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Quimica Fisica Blas Cabrera (IQF-CSIC); University of Bristol; Ministry of Earth Sciences (MoES) - India; Indian Institute of Tropical Meteorology (IITM); Centre for Climate Change Research - India; University of Manitoba; University of Manitoba; Consiglio Nazionale delle Ricerche (CNR); Universita Ca Foscari Venezia; Universite de Lorraine; University of Pennsylvania
摘要：In the polar regions, which are vulnerable receptors of mercury pollution, atmospheric mercury depletion events (AMDEs) efficiently convert elemental mercury (Hg(0)) into oxidized mercury (Hg(II)) via bromine oxidation. Hg(II) subsequently deposits onto snow and sea ice. While field observations have shown that a large percentage of deposited mercury is re-emitted from the ice to the atmosphere by a photoinduced process, the fundamental photochemistry that drives the re-emission process remain...
